The role of medial hypothalamic serotonin in the suppression of feeding in a rat model of colitis.

BACKGROUND & AIMS: Experimental colitis is associated with anorexia that is attenuated by treatment with an interleukin (IL)-1 receptor antagonist. Serotonin (5-hydroxytryptamine [5-HT]) is a potent inhibitor of feeding, and its release from the hypothalamus is stimulated by IL-1. We have tested the hypotheses that anorexia associated with experimental colitis results from increased activity of hypothalamic 5-HT neurons and that the increase in activity occurs secondary to an increase in availability of tryptophan, the precursor of 5-HT. METHODS: In vivo 5-HT release and regional hypothalamic 5-HT and tryptophan concentrations were measured in rats with 2,4,6,-trinitrobenzene sulfonic acid (TNBS)-induced colitis, healthy controls, and animals pair-fed to match the food intake of the colitic group. Food intake in the colitic group was assessed after depletion of brain 5-HT by p-chlorophenylalanine (PCPA). RESULTS: In the colitic group, release of 5-HT from the hypothalamic paraventricular nucleus (PVN) was 3-fold (P = 0.01) and 14-fold (P < 0.001) higher than in control and pair-fed groups, respectively. Concentrations of tryptophan were similar in each group in all hypothalamic regions. Food intake was significantly increased in the colitic group after PCPA treatment but was not restored to control values. CONCLUSIONS: In animals with TNBS-induced colitis, 5-HT release from the PVN is increased. The increase in food intake after depletion of brain 5-HT suggests that hypothalamic 5-HT contributes to anorexia but is not the only mediator. Increased 5-HT release in the colitic group was not driven by increased precursor availability.

Directional tuning of motion-sensitive cells in the anterior superior temporal polysensory area of the macaque.

An investigation was made into the directional sensitivity of cells in the macaque anterior superior temporal polysensory region (STPa) to the motion of objects. The cells studied were sensitive to the presence of motion but showed little or no selectivity for the form of the stimulus. Directional tuning was not continuously distributed about all possible directions. The majority of cells were most responsive to motion in a direction within 15 degrees of one of the three cartesian axes (up/down, left/right, towards/away). Tuning to direction varied in sharpness. For most (34/37) cells the angular change in direction required to reduce response to half maximal was between 45 and 70 degrees (for 3/37 cells it was > 90 degrees). The estimates of the directionality (median Id = 0.97) of STPa cells was similar to that reported for posterior motion processing areas (the middle temporal area, MT, and the medial superior temporal area, MST). The tuning for direction (sharpness, distribution and discrimination) of the motion-sensitive STPa cells were found to be similar to the tuning for perspective view of STPa cells selective for static form of the head and body. On average the STPa responses showed a 100- to 300-ms transient burst of activity followed by a tonic discharge maintained at approximately 20% of the peak firing rate for the duration of stimulation. The responses of motion-sensitive STPa cells occurred at an earlier latency (mean 91 ms) than responses of cells selective for static form (mean 119 ms), but the time course of responses of the two classes of cell were similar in many other respects. The early response latency and directional selectivity indicate that motion sensitivity in STPa cells derives from the dorsal visual pathway via MT/MST. The similarity of tuning for direction and perspective view within STPa may facilitate the integration of motion and form processing within this high-level brain area.

Use of preferential inspection to define the viewing sphere and characteristic views of an arbitrary machined tool part.

Measurements were made of the way human subjects visually inspected an idealized machined tool part (a 'widget') while learning the three-dimensional shape of the object. Subjects were free to rotate the object about any axis. Inspection was not evenly distributed across all views. Subjects focused on views where the faces of the object were orthogonal to the line of sight and the edges of the object were aligned parallel or at right angles to the gravitational axis. These 'face' or 'plan' views were also the easiest for subjects to bring to mind in a mental imagery task. By contrast, when subjects were instructed to imagine the views displaying the most structural information they visualized views lying midway between face views.

Interference of labetalol metabolites in the determination of plasma catecholamines by HPLC with electrochemical detection.

The alpha and beta adrenoceptor blocking drug labetalol is a potent antihypertensive agent in widespread clinical use. Its interference in the classical chemical estimations of urinary catecholamines and their metabolites has been the subject of several reports. Factitiously raised values have been noted in both the fluorimetric catecholamine assay, and the standard spectrophotometric procedure for total (free and conjugated) metadrenalines. To avoid such drug interference, modification of these methods is required in the estimation of catecholamines and their o-methylated metabolites. Alternatively, VMA estimations or plasma/urinary catecholamine measurements by radioenzymatic assay may be used in patients on labetalol. Although high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) methods for estimation of plasma catecholamines are now in widespread use, the interference of labetalol in this method has not been reported. We now report that significant direct interference of labetalol in the HPLC-ECD assay does indeed occur, and can yield spuriously raised adrenaline levels.

Methodological considerations in the determination of plasma catecholamines by high-performance liquid chromatography with electrochemical detection.

We report on a systematic investigation into some frequently encountered problems in the estimation of catecholamines in plasma and biological fluids using high-performance liquid chromatography with electrochemical detection. The kinetics of adsorption and desorption of catecholamines from plasma on to alumina has been studied using laboratory-prepared and some commercial aluminas with various acids. Chromatographic conditions yielding optimal resolution and sensitivity have been characterised. Some possible interfering peaks have been identified. The stability of catecholamines in plasma has been studied.

Neuronal responses related to visual recognition.

To analyse the neural basis of long-term memory, recordings were made from single neurons in monkeys performing a visual recognition task of the type impaired in anterograde amnesia in man. Each visual stimulus was shown twice per day, once as novel, and after 0 to 17 other intervening items in the recognition task, on a second trial, as familiar, when the monkey could lick to obtain fruit juice if he recognized the stimulus correctly. At the anterior border of the thalamus, a population of neurons was found which responded to the stimuli only when they were familiar. The activity of these neurons was not related to lick responses. Further, in a different, visual discrimination, task, a number of these neurons were found to respond both to the familiar rewarded stimulus to which the monkey always licked, and to the familiar aversive stimulus to which he did not lick. This shows that in a reward association task these neurons respond on the basis of familiarity, providing evidence for a dissociation of recognition and associative memories. Analysis of the responses of these neurons in the continuous visual recognition task showed that the responses to familiar stimuli were time-locked to the onset and duration of the visual stimulation (brief exposures producing brief responses). The response latencies were in the range 100 to 200 ms. A 100 ms exposure of the stimulus was sufficient for the stimulus to be encoded, and a 100 ms exposure was also sufficient for a recognition related response. The magnitude of the neuronal response on trials with familiar stimuli decreased as the number of trials between the first (novel) and second (familiar) presentation of the same stimulus increased. The rate of this decay or 'forgetting' varied from cell to cell and was best described by an exponential function. Repeated exposure tended to slow the rate of forgetting, and two or three repeated presentations prolonged some cell 'memories' for more than 100 intervening trials. Although the majority of the neurons did not have such long 'memories', in that they responded as novel to stimuli seen on a preceding day, so that their responses could be related to recency but not to absolute recognition of ever having seen a stimulus before, 2 neurons did respond to stimuli which had not been seen for 24 h. The neurons showed some ability to respond to stimuli as familiar despite changes in viewing conditions and transformations such as 90 deg rotation. These findings indicate that the responses of these neurons at the anterior border of the thalamus are activated during recency or longer term recognition processing, both of which are impaired in anterograde amnesia in man. Measurement of the responses of these neurons, which appear to have access to memory mechanisms, has allowed parameters affecting such memory mechanisms to be investigated.